Respiratory and immune response to maximal physical exertion following exposure to secondhand smoke in healthy adults

© 2012 The Authors. Published by PLOS. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1371/journal.pone.0031880We assessed the cardiorespiratory and immune response to physical exertion following secondhand smoke (SHS) exposure through a randomized crossover experiment. Data were obtained from 16 (8 women) non-smoking adults during and following a maximal oxygen uptake cycling protocol administered at baseline and at 0-, 1-, and 3- hours following 1-hour of SHS set at bar/restaurant carbon monoxide levels. We found that SHS was associated with a 12% decrease in maximum power output, an 8.2% reduction in maximal oxygen consumption, a 6% increase in perceived exertion, and a 6.7% decrease in time to exhaustion (P<0.05). Moreover, at 0-hours almost all respiratory and immune variables measured were adversely affected (P<0.05). For instance, FEV 1 values at 0-hours dropped by 17.4%, while TNF-α increased by 90.1% (P<0.05). At 3-hours mean values of cotinine, perceived exertion and recovery systolic blood pressure in both sexes, IL4, TNF-α and IFN-γ in men, as well as FEV 1/FVC, percent predicted FEV 1, respiratory rate, and tidal volume in women remained different compared to baseline (P<0.05). It is concluded that a 1-hour of SHS at bar/restaurant levels adversely affects the cardiorespiratory and immune response to maximal physical exertion in healthy nonsmokers for at least three hours following SHS. © 2012 Flouris et al.Published versio

Determination of DNA damage and telomerase activity in stanozolol-treated rats

Anabolic androgenic steroids (AAS) are performance -enhancing drugs commonly abused by atheletes. Stanozolol is a synthetic testosterone-derived anabolic steroid. Although it is well known that AAS have several side-effects, there are only few toxicological studies available on the toxic effects and mechanisms of action of stanozolol. The aim of this study was to investigate the genotoxic effects of stanozolol and to determine its effects on telomerase activity in Sprague-Dawley male rats. For this purpose, 34 male rats were divided into 5 groups as follows: i) the control group (n=5); ii) the propylene glycol (PG)-treated group (n=5); iii) the stanozolol-treated group (n=8); iv) the PG-treated group subjected to exercise (n=8); and v) the stanozolol-treated group subjected to exercise (n=8). PG is used as a solvent control in our study. Stanozolol (5 mg/kg) and PG (1 ml/kg) were injected subcutaneously 5 days/week for 28 days. After 28 days, the animals were sacrificed, and DNA damage evaluation (comet assay) and telomerase activity assays were then performed using peripheral blood mononuclear cells (PBMCs). Telomerase activity was measured by using the TeloTAGGG Telomerase PCR ELISA PLUS kit. The results of this study revealed that stanozolol treatment induced DNA damage, while exercise exerted a protective effect. Stanozolol treatment without exercise stimulation was associated with a significant increase in telomerase activity in the PBMCs

Porphyridium purpureum microalga physiological and ultrastructural changes under copper intoxication

The present work assessed the effect of copper (Cu) on cell dynamics and structure of the microalga Porphyridium purpureum (Rhodophyta, Bangiophycidae). Ultrastructure of the microalga was investigated and fluorescence of chlorophyll a and phycoerythrin, and content of reactive oxygen species (ROS) were estimated by flow cytometry. The number of cells did not show statistically significant differences at concentrations of 50 and 100 mu g/L of Cu compared to the control, whereas 150 mu g/L of Cu inhibited population growth. The fluorescence of chlorophyll a increased following exposure to Cu 100 mu g/L and fluorescence of phycoerythrin enhanced by Cu 150 mu g/ L. There was no alteration in the above indicators at other concentrations. The content of ROS increased with increasing Cu concentration in a dose-dependent manner. The population size structure was also changed by Cu as the number of cells sized 4-6 mu m was increased in the presence of Cu, especially with Cu 150 mu g/L. Changes in the topography of thylakoids grew larger with Cu concentration

Chemical analysis and hazard identification of the most common electronic cigarette liquids in nine European countries

Background We aimed to detect the composition and reported chemical health hazards of the most common electronic cigarette liquids (e-liquids) in nine European Union (EU) Member States (MS) prior to adoption of the Tobacco Product Directive (TPD). Material and Methods Within the Horizon2020, EUREST-PLUS study, 122 of the most commonly used e-liquids were purchased from 9 EU MS. Chromatography - mass spectrometry and liquid chromatography - mass spectrometry methods were used to analyze the samples. Among the most frequently detected compounds (detected ≥4 times), Danger Globally Harmonized System of Classification and Labelling of Chemicals (GHS) and Warning GHS codes were identified. Results During the samples analysis, several discrepancies in nicotine concentration were detected among the samples from the 9 EU MS. French samples contained an average of 21.9% more nicotine than labelled, while Romanian samples contained an average of 22.5% less nicotine than labelled. In addition, in the 9.8% of the samples, the nicotine concentration exceeded the limit of 20 mg/ml. With regards to the samples’ composition, 171 different compounds were identified and detected 750 times in total while we did not identify samples positive for PAHs or nitrosamines. Finally from the 171 substances, only 5 (10.4%), (Oxime-, methoxy-phenyl, +/-.-.alpha.-Methylbenzyl acetate, 1,3-Dioxolane, 2-butyl-4-methyl-, Melonal and l-Menthyl acetate) were not associated with a Danger GHS and Warning GHS codes. Conclusions As large number of potential harmful compounds was identified, the systematic monitoring and chemical evaluation of e-liquids is necessary in order to protect the consumers’ health. Acknowledgements EUREST-PLUS is a Horizon2020 project conducted by researchers throughout Europe from both the six participating countries as well as other institution partners within Europe and abroad. Partnering organizations include the European Network on Smoking Prevention (Belgium), Kings College London (United Kingdom), German Cancer Research Centre (Germany), University of Maastricht (The Netherlands), University of Athens (Greece), Aer Pur Romania (Romania), European Respiratory Society (Switzerland), the University of Waterloo (Canada), the Catalan Institute of Oncology (Catalonia, Spain), Smoking or Health Hungarian Foundation (Hungary), Health Promotion Foundation (Poland), University of Crete (Greece), and Kantar Public Brussels (Belgium). Funding The EUREST-PLUS Project takes place with the financial support of the European Commission, Horizon 2020 HCO-6-2015 program (EUREST-PLUS: 681109; C. Vardavas) and the University of Waterloo (GT. Fong). Additional support was provided to the University of Waterloo by the Canadian Institutes of Health Research (FDN-148477). GT. Fong was supported by a Senior Investigator Grant from the Ontario Institute for Cancer Research. E. Fernández is partly supported by Ministry of Universities and Research, Government of Catalonia (2017SGR139) and by the Instituto Carlos III and co-funded by the European Regional Development Fund (FEDER) (INT16/00211 and INT17/00103), Government of Spain

Stanozolol administration combined with exercise leads to decreased telomerase activity possibly associated with liver aging

Anabolic agents are doping substances which are commonly used in sports. Stanozolol, a 17-alkylated derivative of testosterone, has a widespread use among athletes and bodybuilders. Several medical and behavioral adverse effects are associated with anabolic androgenic steroids (AAS) abuse, while the liver remains the most well recognized target organ. In the present study, the hepatic effects of stanozolol administration in rats at high doses resembling those used for doping purposes were investigated, in the presence or absence of exercise. Stanozolol and its metabolites, 16--hydroxystanozolol and 3-hydroxystanozolol, were detected in rat livers using liquid chromatography-mass spectrometry (LC-MS). Telomerase activity, which is involved in cellular aging and tumorigenesis, was detected by examining telomerase reverse transcriptase (TERT) and phosphatase and tensin homolog (PTEN) expression levels in the livers of stanozolol-treated rats. Stanozolol induced telomerase activity at the molecular level in the liver tissue of rats and exercise reversed this induction, reflecting possible premature liver tissue aging. PTEN gene expression in the rat livers was practically unaffected either by exercise or by stanozolol administration

Mean ± SD of cardiorespiratory variables for men and women for the statistically significant post-hoc comparisons.

<p>Note:</p>a<p> = statistically significant (P<0.05) difference from previous measurement.</p>b<p> = statistically significant (P<0.05) difference of <i>T</i>₁ or <i>T</i>₃ from <i>T</i>_B.</p>c<p> = statistically significant (P<0.05) difference between sexes for the same measurement.</p><p>Key: _%Max O₂ uptake: percent predicted maximal oxygen uptake; HR: heart rate; SBP, DBP, and MAP: systolic, diastolic and mean arterial blood pressure, respectively; M: men; W: women.</p

Long-term exposure of rabbits to imidaclorpid as quantified in blood induces genotoxic effect

The present in-vivo study focuses on the genotoxic effect of the neonicotinoid pesticide imidacloprid (IMI) in rabbits. The purpose of the study was to establish a possible relationship between exposure to the pesticide (dose and duration) and genotoxicity. Furthermore, an analytical method for the simultaneous determination of IMI and its major metabolite 6-chloronicotinic acid (6-ClNA) in blood was developed and validated. The isolation of the two analytes from blood was performed by liquid-liquid extraction with dichloromethane. Analysis was performed by Liquid Chromatography - Atmospheric Pressure Chemical Ionization - Mass Spectrometry (LC-APCI-MS). The method was applied on the determination of IMI and 6-ClNA in serum samples obtained from rabbits fed with the insecticide at two low doses. Furthermore, parameters of genotoxicity and cytotoxicity were evaluated by measuring binucleated cells with micronuclei (BNMN), micronuclei (MN) and the Cytokinesis Block Proliferation Index (CBPI), in lymphocytes of exposed rabbits. The results revealed a genotoxic effect of IMI for both exposed groups. There were statistically significant differences in the frequencies of BNMN and MN between control and exposed groups but there was no dose-dependence, neither time-dependence of the genotoxic effect for the administered doses. This is the first time that long term exposure to IMI in rabbits was studied for the determination of its genotoxic effect. The genotoxic effect of IMI as it is depicted by the current study is in accordance with previous studies. (C) 2016 Published by Elsevier Ltd

The metabolism of imidacloprid by aldehyde oxidase contributes to its clastogenic effect in New Zealand rabbits

Imidacloprid (IMI) is a systemic, chloro-nicotinyl insecticide classified in Regulation No 1272/2008 of the European Commision as "harmful if swallowed and very toxic to aquatic life, with long-lasting effects". IMI is metabolized in vitro both by aldehyde oxidase (AOX) (reduction) and by cytochrome P450s enzymes (CYPs). In the present study, the AOX inhibitor sodium tungstate dihydrate (ST) was used to elucidate the relative contribution of CYP 450 and AOX metabolic pathways on IMI metabolism, in male rabbits exposed to IMI for two months. To evaluate the inhibition effectiveness, various metabolite concentrations in the IMI and IMI + ST exposed groups were monitored. DNA damage was also evaluated in micronucleus (MN) and single cell electrophoresis (SCGC) assays in both groups, along with oxidative stress (OS) with the inflammatory status of the exposed animals, in order to clarify which metabolic pathway is more detrimental in this experimental setting. A significant increase in the frequency of binucleated cells with MN (BNMN, 105%) and micronuclei (MN, 142%) was observed after exposure to IMI (p 0.05), which indicates no cytotoxic effect. Similarly, comet results show that the IMI group exhibited the highest achieved tail intensity, which reached 70.7% over the control groups, whereas in the IMI + ST groups the increase remained at 48.5%. No differences were observed between all groups for oxidative-stress biomarkers. The results indicate that the AOX metabolic pathway plays a more important role in the systemic toxicity of IMI

Mean ± SD of cytokine production for men and women for the statistically significant post-hoc comparisons.

<p>Note:</p>a<p> = statistically significant (P<0.05) difference from previous measurement.</p>b<p> = statistically significant (P<0.05) difference of <i>T</i>₁ or <i>T</i>₃ from <i>T</i>_B.</p>c<p> = statistically significant (P<0.05) difference between sexes for the same measurement.</p><p>Key: IL4, 5 and 6: interleukins 4, 5 and 6, respectively; TNF-α: tumor necrosis factor alpha; IFN-γ: interferon gamma; M: men; W: women.</p

Mean ± SD of cotinine and lung function for men and women for the statistically significant post-hoc comparisons.

<p>Note:</p>a<p> = statistically significant (P<0.05) difference from previous measurement.</p>b<p> = statistically significant (P<0.05) difference of <i>T</i>₁ or <i>T</i>₃ from <i>T</i>_B.</p>c<p> = statistically significant (P<0.05) difference between sexes for the same measurement.</p><p>Key: FVC: forced vital capacity; FEV₁: forced expiratory volume in 1 second; _%FEV₁: percent predicted FEV₁; PEF: peak expiratory flow; MEF_75%, MEF_50%, MEF_25%: maximum expiratory flow when 75%, 50% and 25% of FVC remains in the lungs, respectively; MVV: maximum voluntary ventilation; RR: respiratory rate; TV: tidal volume; M: men; W: women.</p